Ebola virus (EBOV) and Marburgvirus (MARV) are members of the Filoviridae, a family of viruses classified as “Category A” bioterrorism agents that cause severe hemorrhagic fever in humans and nonhuman primates with high morbidity and mortality rates up to 90% (Sanchez et al., Filoviridae: Marburg and Ebola viruses, p. 1409-1448. In D. M. Knipe, P. M. Howley, D. E. Griffin, M. A. Martin, R. A. Lamb, B. Roizman, and S. E. Straus (ed.), Fields Virology, 5th ed. Philadelphia, Pa.: Lippincott Williams & Wilkins, 2007). After a short incubation period of 4 to 10 days, Filovirus-infected individuals develop an abrupt onset of symptoms that include fever, chills, malaise, and myalgia that are common to many other viral infections. MARV is antigenically stable and exists in only one species, whereas EBOV is more variable and has five species. The Bundibugyo EBOV emerged recently in late 2007 outbreak in Uganda (Towner et al., PLoS Pathog 2008 November; 4(11):e1000212), and is more related to the Ivory Coast than to the Zaire, Sudan, or Reston EBOV species. Zaire EBOV (ZEBOV) is typically associated with the highest lethality. The increased number of outbreaks in Africa and the recent EBOV outbreak in pigs (Normile Science 2009 Jan. 23; 323(5913):451), which raised concerns that livestock could transmit the deadly disease to humans, highlighted the urgency for the development of vaccines and rapid diagnostic tests to contain outbreaks. Vaccines based on the Filovirus glycoprotein (GP) are in preclinical and clinical evaluation, and currently there are no therapeutic agents to treat Filovirus infection. Since licensing of safe and effective Filovirus vaccine could take several more years, diagnosis and quarantine of infected individuals is currently the main tool to limit outbreaks.
Several Filovirus vaccine candidates are currently being developed, including recombinant adenovirus expressing the EBOV GP (Sullivan et al., PLoS Med 2006 June; 3(6):e177; Sullivan et al., Nature 2003 Aug. 7; 424(6949):681-4; and Sullivan et al., Nature 2000 Nov. 30; 408(6812):605-9), recombinant parainfluenza virus (Bukreyev et al., J Virol 2007 June; 81(12):6379-88), recombinant Venezuelan equine encephalitis virus (Pushko et al., Vaccine 2000 Aug. 15; 19(1):142-53), recombinant replication-competent (Feldmann et al., PLoS Pathog 2007 January; 3(1):e2 and Jones et al., Nat Med 2005 July; 11(7):786-90) and -deficient (Halfmann et al., J Virol 2009 April; 83(8):3810-5) vesicular stomatitis virus, and virus-like particles carrying the Filovirus GP (Warfield et al., Proc Natl Acad Sci USA 2003 Dec. 23; 100(26):15889-94 and Warfield et al., J Infect Dis 2007 Nov. 15; 196 Suppl 2:S430-7). Initial studies using baculovirus-expressed Filovirus GP showed partial protection, which could be attributed to the nature of the glycosylation and processing of GP in insect cells (Mellquist-Riemenschneider et al., Virus Res 2003 April; 92(2):187-93).
Despite advances in this regard, a need exists to develop new vaccines against Filoviruse infections. The present invention addresses these and other needs.